Our response to COVID-19

We're supporting people to maintain their wellbeing and manage isolation.

Placebo response

What is placebo response?

Placebo effects in pharmaceutical trials vary widely, with response rates varying from 20% to 70%. The placebo response can include improvement in symptoms and even adverse reactions that have been associated with the antipsychotic being tested. Placebo effects can substantially influence conclusions about the efficacy of antipsychotic medications as they reduce any differences in response to the antipsychotic and the placebo.

What is the evidence for placebo response?

Moderate to high quality evidence found a small to medium-sized improvement in overall symptoms with placebo, however the response to antipsychotics was greater than the response to placebo. The placebo response was greatest in studies with more efficacious drugs, younger samples, shorter illness duration, more severe baseline symptoms, shorter study duration, increased number of study sites, and non-university or non-Veteran Affairs settings.

For people with stable schizophrenia and predominant negative symptoms, there was a small placebo response for negative symptoms which was most apparent in studies with larger numbers of arms in the trials, larger numbers of study sites, and trials with industry sponsorship rather than academic grants.

Around 66% of people receiving placebo also report an adverse event, with the type of event corresponding to the type of antipsychotic. 27% of people receiving placebo reported nervous system disorders, 13% reported gastrointestinal disorders, and 30% reported psychiatric disorders (anxiety, depression, agitation etc). A higher level of schizophrenia symptoms at baseline was associated with more adverse events with placebo.

There was increased placebo response over time, and decreased treatment response over time (1960 to 2014). This may be explained by enrolment of less severely ill patients in newer studies and higher expectations that medications will improve symptoms.

There was greater improvement in symptoms in the placebo arm of studies using last observation carried forward (LOCF) methods than in studies using mixed-effect models for repeated measures (MMRM). Studies involving more countries and studies in outpatient settings had greater placebo response in the analysis of MMRM methods, while studies with shorter study duration showed greater placebo response in the analysis of LOCF methods.

Overall, there was less variability in response to antipsychotics than in response to placebo, with older studies, those with younger patients, higher dose treatments, and greater mean-difference in symptom-change being associated with less variability.

October 2020

Last updated at: 12:23 am, 14th October 2020
To view documentation related to this topic download the files below
Fact Sheet Technical Commentary

NeuRA Libraries

Title Colour Legend:
Green - Topic summary is available.
Orange - Topic summary is being compiled.
Red - Topic summary has no current systematic review available.